The proposed investigation intends to explore if the combination of trabectedin and doxorubicin in the first line of treatment of advanced sarcomas obtains better results than doxorubicin monotherapy. This proposal arises from the need to bring to the first line of treatment of advanced STS agents that have shown activity in second line. The goal is to improve available standard treatments. Tumors in patients not previously exposed to chemotherapy have not been selected in their biological behavior and they are the best scenario to test antitumor activity of a new anticancer drug.

The combination of drugs with different mechanisms of action may be a clear advantage to obtain better results and potential synergy. On the other hand, the toxicity profiles of both study drugs are different and worsening or summative of adverse effects is not expected.

The purpose of this study is to determine the efficacy of the combination of trabectedin and doxorubicin in comparison with doxorubicin alone in patients with advanced non operable and/or metastatic Soft Tissue Sarcomas (STS).

Further study details as provided by Grupo Espanol de Investigacion en Sarcomas:

Primary Outcome Measures:

To determine the efficacy of the combination of trabectedin and doxorubicin in comparison with doxorubicin alone in patients with advanced non operable and/or metastatic Soft Tissue Sarcomas (STS) [ Time Frame: 2012 ] [ Designated as safety issue: No ]

To determine the efficacy of the combination of trabectedin and doxorubicin in comparison with doxorubicin alone in patients with advanced non operable and/or metastatic Soft Tissue Sarcomas (STS). To this end, progression free survival will be compared between both groups of treatment.

Secondary Outcome Measures:

To determine activity by means of RECIST objective responses in both study arms, trabectedin/doxorubicin combination and the control arm. [ Time Frame: 2012 ] [ Designated as safety issue: No ]

To determine activity by means of RECIST objective responses in both study arms, trabectedin/doxorubicin combination and the control arm.

To determine the tumor control (response rates plus stabilizations) in both arms of treatment. [ Time Frame: 2012 ] [ Designated as safety issue: No ]

To determine the tumor control (response rates plus stabilizations) in both arms of treatment.

To determine toxicity of trabectedin/doxorubicin combination and the control arm. [ Time Frame: 2012 ] [ Designated as safety issue: Yes ]

To determine toxicity of trabectedin/doxorubicin combination and the control arm.

To determine protein and mRNA expression of genes possibly involved in a potential profile of more favorable response or resistance to study drugs and to analyze the prognostic impact of them on predefined efficacy parameters. [ Time Frame: 2012 ] [ Designated as safety issue: No ]

To determine protein and mRNA expression of genes possibly involved in a potential profile of more favorable response or resistance to study drugs and to analyze the prognostic impact of them on predefined efficacy parameters.

To evaluate genomic instability, as well as protein expression that could influence response/resistance to the study drugs and make a correlation with efficacy endpoints. [ Time Frame: 2012 ] [ Designated as safety issue: No ]

To evaluate genomic instability, as well as protein expression that could influence response/resistance to the study drugs and make a correlation with efficacy endpoints.

A maximum of 6 cycles every 3 weeks of the combination (Trabectedin 1,1 mg/square meter + doxorubicin 60 mg/square meter) will be given in the absence of progression or not acceptable toxicity.

Eligibility

Ages Eligible for Study:

18 Years to 70 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

The patient must sign voluntarily the informed consent from before any study test is conducted that is not part of routine patient care, with the knowledge that he/she can abandon the study at any time without this affecting his/her previous care.

Men or women of child bearing potential should be using an effective method of contraception before entry into the study and throughout the same and for 6 months after ending the study. Women of childbearing potential must have a negative urine pregnancy test before study entry.

Previous radiotherapy involving the only localization(s) of measurable tumoral disease.

Performance status> 2 Eastern Cooperative Oncology Group(ECOG).

Central Nervous System (CNS) metastases.

Plasma bilirubin > upper limit of normal(ULN).

Creatinine > 1.6 mg/dL.

History of other neoplastic disease with the exception of basalioma or in situ cervical cancer adequately treated.

Significant cardiovascular disease (for example, dyspnea > 2 NYHA)

Significant systemic diseases grade 3 or higher on the NCI-CTC version 3.0 scale, that limit patient availability, or according to investigator judgment may contribute significantly to treatment toxicity.

Uncontrolled bacterial, mycotic or viral infections.

Women who are pregnant or breast-feeding

Psychological, familial, social or geographic circumstances that limit the patient's ability to comply with the protocol or informed consent.

Patients participating in another clinical trial or receiving any other investigational product.

Patients who had participated in another clinical trial and/or had received any other investigational product in the last 30 days prior to inclusion.

The following histologic subtypes are excluded:

Rhabdomyosarcoma

Ewing's family of tumors

Desmoplastic small round cell tumor

Clear cell sarcoma

Alveolar sarcoma

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01104298